Figure 7. Sox17 expression in β cells improves glycemic control and islet architecture but not glucose clearance in MODY4 (Pdx1t^TA/+) animals.

A, B) Tetracycline-regulated expression of Sox17 in Pdx1t^TA/+ animals. Sox17 levels in Pdx1 haploinsufficient animals (Pdx1t^TA/+) were compared to animals with transgenic Sox17 overexpression driven by the Pdx1^tTA/+ allele (Pdx1^tTA/+;TetO-Sox17). Activation of the TetO-Sox17 transgene by removal of doxycycline resulted in a 2–3 fold increase in Sox17 protein over Pdx1^tTA/+ control animals. Scale bar: 15 µm for A and 20 µm for B. C, D) Non-fasting blood glucose levels in control (TetO-Sox17), Pdx1^tTA/+, and Pdx1t^TA/+;TetO-Sox17 mice on doxycycline (Sox17 OFF, n = 3) and off doxycycline (Sox17 ON, n = 3) for 8 days. E) Non-fasting plasma insulin levels were low in Pdx1t^TA/+ animals compared to controls. Sox17 expression restored serum insulin to control levels. F–O) Islet architecture was disrupted in Pdx1^tTA/+ animals, with glucagon (+) cells in the core of the islet. The islet architecture was more normal appearing following 13 weeks of Sox17 expression in Pdx1t^TA/+ animals. Scale bar: 50 µm. P) Sox17 did not restore the ability of Pdx1^tTA/+ animals to respond to a glucose challenge (Pdx1-tTA;tetO-Sox17 mice – n = 3, off Dox; Pdx1-tTA – n = 2, on Dox and n = 1, off Dox; tetO-Sox17– n = 2, on Dox and n = 1, off Dox).